Identification of Bcl-6-dependent follicular helper NKT cells that provide cognate help for B cell responses

Pheh Ping Chang, Patricia Barral, Jessica Fitch, Alvin Pratama, Cindy S. Ma, Axel Kallies, Jennifer J. Hogan, Vincenzo Cerundolo, Stuart G. Tangye, Robert Bittman, Stephen L. Nutt, Robert Brink, Dale I. Godfrey, Facundo D. Batista, Carola G. Vinuesa*

*Corresponding author for this work

    Research output: Contribution to journalArticlepeer-review

    247 Citations (Scopus)

    Abstract

    Lipid antigens trigger help from natural killer T cells (NKT cells) for B cells, and direct conjugation of lipid agonists to antigen profoundly augments antibody responses. Here we show that in vivo, NKT cells engaged in stable and prolonged cognate interactions with B cells and induced the formation of early germinal centers. Mouse and human NKT cells formed CXCR5+ PD -1 hi follicular helper NKT cells (NKTFH cells), and this process required expression of the transcriptional repressor Bcl-6, signaling via the coreceptor CD28 and interaction with B cells. NKTFH cells provided direct cognate help to antigen-specific B cells that was dependent on interleukin 21 (IL-21). Unlike T cell-dependent germinal centers, those driven by NKTFH cells did not generate long-lived plasma cells. Our results demonstrate the existence of a Bcl-6-dependent subset of NKT cells specialized in providing help to B cells.

    Original languageEnglish
    Pages (from-to)35-43
    Number of pages9
    JournalNature Immunology
    Volume13
    Issue number1
    DOIs
    Publication statusPublished - Jan 2012

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